Photobiological activity of 3,4'-dimethyl-8-methoxypsoralen, a linear furocoumarin with unusual DNA-binding properties.
The furocoumarin derivative 3,4'-dimethyl-8-methoxypsoralen (DMe-8-MOP) exhibits remarkable antiproliferative activity, but is devoid of skin phototoxicity. To gain insight into this peculiar behaviour we investigated non-covalent and covalent binding of DMe-8-MOP to calf thymus DNA, along with DNA-synthesis inhibition and mutagenic activity. The non-covalent interaction of DMe-8-MOP with the nucleic acid is quite poor as shown by equilibrium dialysis, spectroscopic, chiroptical and hydrodynamic techniques. However, it exhibits relevant photobinding ability to DNA using both isolated nucleic acid samples and cellular systems. Unlike the large majority of congeners, DMe-8-MOP undergoes predominantly photochemical monoaddition to the double helical polynucleotide. Upon examination of the products obtained by enzymatic hydrolysis of DMe-8-MOP photomodified DNA, the formation of an unusual furan side adduct is proposed, which could account for the peculiar photochemical and photobiological properties of the 3,4'-dimethyl furocoumarin derivative.
Palumbo
M
M
Department of Organic Chemistry, Biopolymer Research Centre, Padova, Italy.
Baccichetti
F
F
Antonello
C
C
Gia
O
O
Capozzi
A
A
Magno
S M
SM
D000818:Animals; D002417:Cattle; D004247:DNA / Q000378:metabolism* / Q000528:radiation effects; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D004926:Escherichia coli / Q000187:drug effects; D008730:Methoxsalen / Q000378:metabolism* / Q000494:pharmacology / Q000031:analogs & derivatives; D009152:Mutagenicity Tests; D011838:Radiation-Sensitizing Agents / Q000378:metabolism*; D013950:Thymus Gland; D014466:Ultraviolet Rays
D011838:Radiation-Sensitizing Agents; C067111:3,4'-dimethyl-8-methoxypsoralen; D004247:DNA; D008730:Methoxsalen